Heterogeneity of thyroid function and impact of peripheral thyroxine deiodination in centenarians and semi-supercentenarians: association with functional status and mortality

Thyroid hormones (FT3, FT4) and TSH were evaluated in a population of 672 well-characterized Italian subjects (age range: 52-113 years), including an unprecedented number of centenarians, semi-supercentenarians, as well as centenarian's offspring and age-matched elderly (CENT, 105+, CENTOFF and CTRL, respectively). The results show that FT3 level and FT3/FT4 ratio decrease while FT4 and TSH increase in an age-dependent manner. In CENT/105+, higher FT4 level and lower FT3/FT4 ratio are associated with an impaired functional status and an increased mortality. A cluster analysis identified three clusters of CENT/105+ based on their FT3, FT4 and TSH levels. Cluster3, characterized by lower FT3 and TSH and higher FT4, shows the worst health status and the shortest survival. Thus, the age-related changes of thyroid hormones extend to the most advanced age and CENT/105+ are highly heterogeneous regarding thyroid function. This heterogeneity is related to different health, functional and cognitive status, as well as with survival/mortality in CENT/105+. Finally, we investigated a remarkable number of CENT/105+ showing a thyroid profile suggestive of non-thyroidal illness syndrome (NTIS) (excluded from the previous analysis). NTIS CENT/105+ are characterized by a worse functional and cognitive status and an increased mortality with respect to CENT/105+ without NTIS.